Citrulline / L-Citrulline

ID: l_citrulline

Aliases: citrulline, citrulline malate, watermelon citrulline, L-citrulline, L-Citrulline, Citrulline

Type: compound

Route/form: oral supplement in human studies

Status: supplement

Evidence level: human RCT

Best data tier: human controlled/review

Support scope: human, non-human/mechanistic

Source types: meta_analysis, preclinical

Linked sources: 4

Broad outcomes: Cardiovascular / lipids / blood pressure, Fat loss / metabolic health, Gut / immune / inflammation, Longevity / mitochondrial / redox, Muscle growth / performance / recovery, mTORC / autophagy / nutrient signaling

Reading note: These are curation notes anchored to linked sources, not a clinical recommendation or protocol.

Targets / mechanism

• arginine/nitric oxide precursor
• urea cycle intermediate
• macrophage mTOR-HIF1A-glycolysis inflammatory metabolism in mice

Optimization domains

• cardiovascular health
• blood pressure
• exercise performance
• inflammation
• anti aging
• metabolic
• mTOR-HIF1A signaling
• nitric oxide
• pump
• vascular performance

Research basis

• Citrulline is already one of the better-supported supplement entries here: meta-analyses cover blood pressure, endurance/performance context, and citrulline malate repetition performance rather than only mechanistic nitric-oxide claims.
• Human meta-analyses support a plausible blood-pressure and exercise-performance evidence base for oral citrulline/citrulline malate.
• The 2025 Science Advances mouse paper adds a separate mechanistic lead around macrophage metabolism, inflammaging, and mTOR-HIF1A-glycolysis.

Limits, risks, and missing evidence

• Exercise and blood-pressure effects are modest and protocol/population dependent.
• The macrophage-aging paper is mouse/mechanistic and should not be merged with gym-pump or BP claims as if it were a human anti-aging trial.
• L-citrulline, citrulline malate, and watermelon/food-source studies should not be collapsed into the same dose or effect-size claim.

Risk flags

• modest effect size
• protocol dependent
• bp interaction context
• formulation specific

Linked papers, labels, and reviews

1. Effects of L-citrulline supplementation on blood pressure: A systematic review and meta-analysis
   meta_analysis / pubmed_lcitrulline_bp_meta_2019
   Human clinical-trial meta-analysis; supports modest oral citrulline blood-pressure signal with dose/population caveats.
2. Effect of food sources of nitrate, polyphenols, L-arginine and L-citrulline on endurance exercise performance
   meta_analysis / pubmed_lcitrulline_exercise_meta_2021
   Systematic review/meta-analysis of randomized trials for nitric-oxide-related food compounds including L-citrulline and exercise performance.
3. Acute Effect of Citrulline Malate on Repetition Performance During Strength Training: A Systematic Review and Meta-Analysis
   meta_analysis / pubmed_lcitrulline_strength_meta_2021
   Human strength-training meta-analysis for citrulline malate repetition performance; useful for gym-performance claims.
4. Citrulline regulates macrophage metabolism and inflammation to counter aging in mice
   preclinical / pmc_citrulline_macrophage_aging_2025
   Science Advances mouse/mechanistic source linking citrulline to macrophage metabolism, inflammation, and aging phenotypes.